Loss of the Angiopoietin-1 protein increases kidney fibrosis

2018-01-08

Patients with chronic kidney disease present a progressive decline in kidney function. Independent of its underlying cause, fibrosis in the kidney, i.e an excess of connective tissue, is predictive of the kidney function decline. A recent study from IGP shows a correlation between the protein Angiopoietin-1 and fibrosis development in mouse kidneys. This suggests that manipulations to maintain Angiopoietin-1 levels could slow down fibrosis progression.

Approximately 13 per cent of the Swedish population has chronic kidney disease, which results in higher morbidity and mortality, especially in cardiovascular diseases. In end stage renal disease, when the kidneys cannot maintain enough function for the body, the only treatments available are dialysis or kidney transplant. There is neither any effective treatment for the fibrosis that is associated with the loss of kidney function.

The protein Angiopoietin-1 (Angpt1) stabilizes the cells that line the inside of blood vessels. Injury to the small blood vessels in the kidney is suggested to be a major factor in the progression of fibrosis.

“To investigate the role of Angpt1 we generated mice that lack the gene that encodes the Angpt1 protein. When these mice were exposed to a treatment that induces kidney fibrosis we saw an increase in kidney fibrosis in Angpt1 deficient mice compared to control mice after the same treatment. These results suggest a worsening of kidney injury when Angpt1 is missing,” says Marie Jeansson, researcher at IGP, who has led the study.

The researchers also studied the blood vessels in fibrosis and found that Angpt1 deficient mice had fewer vessels.

“Our results suggest that loss of blood vessels occurs before development of fibrosis and that Angpt1 can affect this. As there is currently no treatment for kidney fibrosis, it is important to understand and identify factors that regulate the fibrotic process as they might be targets for treatment of kidney disease. One such target could be Angpt1,” says Marie Jeansson.

The results have been published in PLOS ONE and is a collaboration with researchers at Uppsala University, Karolinska Institutet, and Northwestern University.